The Oregon National Primate Research Center (ONPRC) proposes to continue a Specialized Cooperative (U54) Center in Reproduction Research that addresses the causes and cures of human fertility disorders as related to neural, gonadal and gamete deficits. Each research project utilizes female nonhuman primates in translational research, and two contain clinical components in an effort to relate new information to improving women's health. Project I, "Effect of Common Life Stresses on Fertility", expands investigations on the neuroendocrine and gonadal lesions associated with a combination of mild, acute forms of stress (e.g., dieting and psychosocial changes) and whether treatment to increase serotonergic tone ameliorates these lesions, as well as associated infertility. Project II, "Novel Mechanisms Underlying the Transsynaptic Control of LHRH Release", continues genetic and cellular manipulations to evaluate the role of GABA input, as well as that of other novel genes (FXYD, Nell2, and lAP-l) in upstream neuronal pathways, in controlling the function of LHRH neurons and normal reproductive cyclicity. Project III, "Angiogenic and Angiolytic Factors in Natural and Controlled Ovarian Stimulation (COS) Cycles", will examine the expression and action of angiopoietin (Ang) and endocrine gland (EG)-VEGF in the preovulatory follicle and corpus luteum, and whether alterations in Ang, EG-VEGF, as well as VEGF-A, cause ovarian disorders, such as ovarian hyperstimulation syndrome (OHSS). Project IV, "Proteomic Profiling: Markers of Normal and Abnormal Follicle Development", is a pilot project to determine the feasibility of using proteomic analyses of follicular fluid to identify novel proteins involved in follicular development and ovulation, as well as markers or mechanisms in polycystic ovarian syndrome (PCOS). Thus, all projects attempt to relate basic reproductive processes to the etiology and/or treatment of infertility. These projects will be supported by three core laboratories (Assisted Reproductive Technologies or ART, Core A;Imaging &Morphology or IM, Core B;Molecular &Cellular Biology or MCB, Core C) operating in an "open access" formula. The Administrative Core will foster intra- and inter-center cooperation in basic and applied research. The ONPRC U54 Center is flourishing through a strong scientific environment at the Primate Center, collaborations in women's health at the Oregon Health &Science University, and interactions with other SCCPRR programs.